Characterization of Theiler's murine encephalomyelitis virus (TMEV)-specific delayed-type hypersensitivity responses in TMEV-induced demyelinating disease: correlation with clinical signs.
Population
Susceptible SJL/J mice and resistant BALB/c mice
Comparison
Intracerebral inoculation of Theiler's murine… vs Comparison between susceptible and resistant…
Design
Preclinical
Follow-up
up to 6 months
Authors
Discussion
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Implication
TMEV DTH responses may mark demyelination susceptibility in mice; leaves open translation to human MS pathogenesis.
Key Points
- To determine whether a temporal correlation exists between the onset of clinical demyelinating disease and the development of virus-specific cellular versus humoral immune responses in susceptible and resistant mice.
- Inoculated susceptible SJL/J and resistant BALB/c mouse strains intracerebrally with Theiler's murine encephalomyelitis virus (TMEV).
- Monitored the onset of clinical disease while tracking TMEV-specific delayed-type hypersensitivity (DTH), T cell proliferative responses, and serum antibody levels over a 6-month period.
- Characterized the phenotype and MHC class restriction of reactive T cells mediating DTH and proliferation in susceptible mice.
- Susceptible SJL/J mice developed TMEV-specific DTH and T cell proliferation within 10 to 14 days post-infection, preceding clinical signs and persisting for 6 months, whereas resistant BALB/c mice exhibited minimal proliferation and no detectable DTH.
- Both mouse strains generated equivalent levels of TMEV-specific serum antibodies with identical temporal kinetics.
- Cellular immune responses in SJL/J mice were mediated exclusively by virus-specific, L3T4+, Lyt-1+2-, class II-restricted T cells.
Structured PICO
P
Population
Susceptible SJL/J mice and resistant BALB/c mice
I
Intervention
Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV)
C
Comparator
Comparison between susceptible (SJL/J) and resistant (BALB/c) strains
O
Outcome
Development of TMEV-specific delayed-type hypersensitivity (DTH) and T cell proliferative (Tprlf) responses, and onset of clinical signssurrogate
TMEV-specific delayed-type hypersensitivity responses correlate with the onset of clinical demyelinating disease in susceptible mouse strains, supporting an immune-mediated mechanism for myelin breakdown.
Cite This Study
Clatch et al. (1986) studied this question.